Relapsed or Refractory Anaplastic Large-cell Lymphoma, Relapsed or Refractory Hodgkin Lymphoma
Conditions
Keywords
Pediatric, Lymphoma, Hodgkin, Anaplastic Large-cell, Relapsed, Refractory, Drug therapy
Brief summary
The purpose of this study is to assess the safety and pharmacokinetics, and determine the pediatric maximum tolerated dose and/or or recommended phase 2 dose of brentuximab vedotin.
Detailed description
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat children who have relapsed or refractory (r/r) anaplastic large-cell lymphoma (sALCL) or Hodgkin lymphoma (HL). This study will look at the maximum tolerated dose and/or recommended phase 2 dose, safety and pharmacokinetics of brentuximab vedotin along with overall response of people who took brentuximab vedotin. The study enrolled 36 patients. In the phase 1 portion of the study, 12 participants were enrolled to receive brentuximab vedotin 1.4-1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. Once the maximum tolerated dose and/or recommended phase 2 dose and pharmacokinetics of brentuximab vedotin was reached, participants were enrolled by diagnosis into two phase 2 study arms: relapsed or refractory sALCL or relapsed or refractory HL and received brentuximab vedotin 1.8 mg/kg as 30-minute IV on Day 1 of every 21-day cycle for up to 16 cycles. One participant received a maximum of 20 cycles at the joint discretion of the sponsor and the investigator for continued clinical benefit. This multicenter trial is being conducted worldwide. The overall time to participate in this study is approximately 5 years. Participants made multiple visits to the clinic, and were contacted by telephone every 12 weeks for 12 months after the end of treatment (EOT) for progression free survival and then every 6 months until death, study closure, or 2 years after enrollment of the last participant for overall survival.
Interventions
DRUGBrentuximab vedotin
Brentuximab vedotin IV infusion
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants aged 2 to \<18 years (5 to \<18 years for Hodgkin lymphoma \[HL\]) * Diagnosis of systemic anaplastic large-cell lymphoma (sALCL), or HL for which standard, curative, life-prolonging, or palliative treatment does not exist or is no longer effective * Participants with sALCL must have documented anaplastic lymphoma kinase (ALK) status and must be beyond first remission or refractory to front-line chemotherapy * Participants diagnosed with any relapsed or refractory CD30+ hematologic malignancy (e.g., primary mediastinal B-cell lymphoma) may be included in phase 1 of the study * Participants with HL must be in their second of later relapse, have failed systemic chemotherapy either as induction therapy for advanced stage disease or salvage therapy, and were ineligible for, refused, or previously received a stem cell transplant * Performance score ≥ 60 from Lansky Play Performance Scale if ≤16 years * Negative pregnancy test * Fertile Participants must use 2 effective methods of contraception prior to and through 6 months after the last dose of the study drug
Exclusion criteria
* Current diagnosis of primary cutaneous ALCL (those with systemic ALCL are eligible) * Received an allogeneic stem cell transplant \<3 months prior to the first dose of study medication, or presence of polymerase chain reaction (PCR)-detectable cytomegalovirus (CMV) in any post-allogeneic transplant participant * Receiving immunosuppressive therapy * Receiving systemic therapy for chronic graft-versus-host disease (topical therapy is allowed) * Previous treatment with any anti-CD30 antibody * Therapeutic monoclonal antibody use within the longer of 6 weeks or 5 plasma half-lives * Systemic cardiac disease that would, in the opinion of the investigator or medical monitor, interfere with assessment of efficacy or safety of the drug * History of another primary malignancy not in remission for at least 3 years (the following are exempt from the 3-year limit: nonmelanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear) * Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML * History of cirrhosis * Active systemic viral, bacterial, or fungal infection requiring antimicrobial, antiviral therapy or antifungal therapy within 2 weeks prior to the first dose of study drug (routine antimicrobial prophylaxis is acceptable) * Concurrent therapy with other anti-neoplastic or experimental agents * Systemic corticosteroid therapy \<7 days prior to first dose of the study medication * Any serious underlying medical condition that, in the opinion of the investigator or medical monitor, would impair their ability to receive or tolerate the planned treatment * Known hypersensitivity to recombinant proteins, murine proteins, or any excipient contained in the drug formulation * Received nitrogen mustard agents, melphalan, or BCNU therapy within 6 weeks prior to the first study dose * Prior autologous hematopoietic stem cell infusion \<4 weeks prior to first study dose * Grade 2 or greater unresolved toxicity from prior antineoplastic therapy * Grade 2 or greater peripheral neuropathy * Female participants who are both lactating and breastfeeding, or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug * Received local palliative radiation therapy \<14 days prior to the first dose of study medication * Received radiation therapy to more than 25% of the bone marrow-containing spaces \< 84 days prior to first dose of study medication * Received a strong or listed moderate inhibitor of CYP3A4 \<2 weeks prior to first study dose * Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1) | From the first dose through 30 days after the last dose of study medication (Up to 15 months) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. |
| Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | From the first dose through 30 days after the last dose of study medication (Up to 15 months) | Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention. |
| Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1) | From the first dose through 30 days after the last dose of study medication (Up to 15 months) | Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature. |
| Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1) | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose | Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate. |
| Serum Concentration of Total Antibodies (Conjugated and Unconjugated) (Phase 1) | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose | Blood samples were collected and tested for conjugated and unconjugated antibodies. |
| Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1) | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose | Blood samples were collected and tested for MMAE plasma concentrations. |
| Overall Response Rate (ORR) (Phase 1 and 2) | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or end of treatment (EOT) (Up to 15 months) | Overall response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) (Phase 1 and 2) | Every 6 months after EOT, until the sooner of death, study closure, or 2 years after enrolment of the last participant (Up to 72 months) | OS is the time in months from start of study treatment to date of death due to any cause. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) | From the first dose through 30 days after the last dose of study medication (up to 15 months) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. |
| Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | From the first dose through 30 days after the last dose of study medication (Up to 15 months) | Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention. |
| Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) | Baseline up to EOT (Up to 15 months) | Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA and nATA development) using a laboratory test. ATA-positive samples were further characterized as transiently ATA positive (defined as 1 or 2 post-Baseline ATA-positive responses), persistently ATA positive (defined as more than 2 post-Baseline ATA positive responses), and nATA positive or negative. |
| Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose | Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate. |
| Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose | Blood samples were collected and tested for conjugated and unconjugated antibodies. |
| Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose | Blood samples were collected and tested for MMAE plasma concentrations. |
| Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2) | From the first dose through 30 days after the last dose of study medication (Up to 15 months) | Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature. |
| Overall Response Rate (ORR) (Phase 1) | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months) | Overall response rate is defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. |
| Time to Progression (TTP) (Phase 1 and 2) | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months) | TTP is defined as the time in months from first dose until the first subsequent documentation of objective tumor progression. Progressive disease (PD) is defined as any new lesion or increase by ≥50% of previously involved sites from nadir. |
| Time to Response (Phase 1 and 2) | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months) | Time to response is defined as the time in months from the first dose of study treatment until the date of the first assessment of confirmed CR or PR. as assessed by an IRF using IWG revised response criteria for malignant lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. |
| Duration of Response (DOR) (Phase 1 and 2) | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months) | DOR is defined as the time in months from the date of first documentation of a CR or PR to the date of first documentation of tumor progression or PD per IRF assessment according to IWG criteria or to death due to any cause, whichever comes first. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir. |
| Event Free Survival (EFS) (Phase 1 and 2) | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months) | EFS is defined as the time in months from first dose until any cause of treatment failure: disease progression, premature discontinuation of treatment for any reason, or death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir. |
| Progression Free Survival (PFS) (Phase 1 and 2) | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months) | PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir. |
Countries
France, Germany, Italy, Mexico, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 12 investigative sites in United States, France, Germany, Netherlands, United Kingdom, Italy, Spain and Mexico from 16-April-2012 to 12-April-2018.
Pre-assignment details
Participants with diagnosis of relapsed or refractory (r/r) sALCL/HL were enrolled to receive brentuximab vedotin 1.4-1.8 mg/kg, intravenous infusion on Day 1 of every 21-day cycle for up to 16 cycles. Treatment beyond 16 cycles was permitted at joint discretion of sponsor and investigator for participants experiencing continued clinical benefit.
Participants by arm
| Arm | Count |
|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | 3 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | 16 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | 17 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Alive at Last Follow-up | 0 | 6 | 11 |
| Overall Study | Completed Post Treatment Followup (PTFU) | 2 | 0 | 1 |
| Overall Study | Death | 1 | 6 | 2 |
| Overall Study | Withdrawal by Patient | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Total | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only |
|---|---|---|---|---|
| Age, Continuous | 14.7 years STANDARD_DEVIATION 1.15 | 13.1 years STANDARD_DEVIATION 3.19 | 11.5 years STANDARD_DEVIATION 3.18 | 14.5 years STANDARD_DEVIATION 2.68 |
| Body Surface Area | 1.562 m^2 STANDARD_DEVIATION 0.0967 | 1.469 m^2 STANDARD_DEVIATION 0.3228 | 1.313 m^2 STANDARD_DEVIATION 0.3103 | 1.617 m^2 STANDARD_DEVIATION 0.2938 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 4 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 29 Participants | 12 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Height | 167.17 cm STANDARD_DEVIATION 10.865 | 158.02 cm STANDARD_DEVIATION 17.493 | 149.54 cm STANDARD_DEVIATION 17.783 | 165.31 cm STANDARD_DEVIATION 14.35 |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 31 Participants | 16 Participants | 13 Participants |
| Region of Enrollment France | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Germany | 0 Participants | 5 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Italy | 1 Participants | 14 Participants | 6 Participants | 7 Participants |
| Region of Enrollment Mexico | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Netherlands | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Spain | 0 Participants | 4 Participants | 4 Participants | 0 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 1 Participants | 11 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 25 Participants | 14 Participants | 9 Participants |
| Weight | 53.10 kg STANDARD_DEVIATION 9.924 | 50.04 kg STANDARD_DEVIATION 17.361 | 42.16 kg STANDARD_DEVIATION 15.162 | 57.85 kg STANDARD_DEVIATION 17.539 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 6 / 16 | 2 / 17 |
| other Total, other adverse events | 3 / 3 | 16 / 16 | 17 / 17 |
| serious Total, serious adverse events | 0 / 3 | 7 / 16 | 1 / 17 |
Outcome results
Primary
Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1)
Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose
Population: Data for this outcome measure was not summarized for Phase 1 participants only, data was summarized together for Phase 1 and 2 participants in brentuximab 1.4 mg/kg and 1.8 mg/kg arms groups. Data has been presented in OM 19.
Primary
Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1)
Blood samples were collected and tested for MMAE plasma concentrations.
Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose
Population: Data for this outcome measure was not summarized for Phase 1 participants only, data was summarized together for Phase 1 and 2 participants in brentuximab 1.4 mg/kg and 1.8 mg/kg arms groups. Data has been presented in OM 21.
Primary
Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1)
Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
Time frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months)
Population: Safety population is defined as all participants who received at least 1 dose of study drug. Participants enrolled in Phase 1 of study were evaluated for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Hyperuricaemia | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Transaminases increased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Lymphocyte count decreased | 1 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Neutrophil count decreased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Blood bicarbonate decreased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Weight decreased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Hypocalaemia | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Gamma-glutamyltransferase increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Weight decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Gamma-glutamyltransferase increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Blood bicarbonate decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Transaminases increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Hyperuricaemia | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Lymphocyte count decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Hypocalaemia | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) | Neutrophil count decreased | 1 Participants |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Time frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months)
Population: Safety population is defined as all participants who received at least 1 dose of study drug. Participants enrolled in Phase 1 of study were evaluated for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1) | TEAE | 3 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1) | SAE | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1) | SAE | 4 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1) | TEAE | 9 Participants |
Primary
Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1)
Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.
Time frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months)
Population: Safety population is defined as all participants who received at least 1 dose of study drug. Participants enrolled in Phase 1 of study were evaluated for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1) | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1) | 0 Participants |
Primary
Overall Response Rate (ORR) (Phase 1 and 2)
Overall response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or end of treatment (EOT) (Up to 15 months)
Population: Response-evaluable population included participants who received at least 1 dose of study drug, have measurable disease at baseline, and 1 postbaseline disease assessment. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Overall Response Rate (ORR) (Phase 1 and 2) | 0 percentage of participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Overall Response Rate (ORR) (Phase 1 and 2) | 47 percentage of participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Overall Response Rate (ORR) (Phase 1 and 2) | 53 percentage of participants |
Primary
Serum Concentration of Total Antibodies (Conjugated and Unconjugated) (Phase 1)
Blood samples were collected and tested for conjugated and unconjugated antibodies.
Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose
Population: Data for this outcome measure was not summarized for Phase 1 participants only, data was summarized together for Phase 1 and 2 participants in brentuximab 1.4 mg/kg and 1.8 mg/kg arms groups. Data has been presented in OM 20.
Secondary
Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2)
Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose
Population: PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Cycle 2 Day 2 values are collected in phase 1 participants only. Here, number analyzed is number of participants assessed at given time-point. Data summarized together for all participants in brentuximab vedotin 1.8 mg/kg arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 2 Day 3, 48 Hours Post-Dose | 3.70 ug/mL | Standard Deviation 1.95 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 2 Day 2, 24 Hours Post-Dose | 8.80 ug/mL | Standard Deviation 6.19 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 2 Day 5, 96 Hours Post-Dose | 2.04 ug/mL | Standard Deviation 1.26 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 6 Day 1, Pre-Dose | 0.312 ug/mL | Standard Deviation 0.351 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 3 Day 1, Pre-Dose | 0.116 ug/mL | Standard Deviation 0.163 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 3, 48 Hours Post-Dose | 5.67 ug/mL | Standard Deviation 0.924 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 5 Day 1, Pre-Dose | 0.264 ug/mL | Standard Deviation 0.321 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 6 Day 1, 5 minutes Post-Dose | 20.3 ug/mL | Standard Deviation 4.38 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 7 Day 1, 5 minutes Post-Dose | 17.9 ug/mL | Standard Deviation 2.4 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 3 Day 1, 5 minutes Post-Dose | 23.9 ug/mL | Standard Deviation 2.83 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 7 Day 1, Pre-Dose | 0.327 ug/mL | Standard Deviation 0.337 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 2 Day 1, 5-minutes Post-Dose | 25.3 ug/mL | Standard Deviation 7.56 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 4 Day 1, Pre-dose | 0.218 ug/mL | Standard Deviation 0.271 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 1, 5 Minutes Post-Dose | 23.1 ug/mL | Standard Deviation 3.46 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 14, 312 Hours Post-Dose | 0.844 ug/mL | Standard Deviation 0.309 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 2, 24 Hours Post-Dose | 9.50 ug/mL | Standard Deviation 1.73 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 5, 96 Hours Post-Dose | 3.50 ug/mL | Standard Deviation 1.41 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 2 Day 1, Pre-Dose | 0.149 ug/mL | Standard Deviation 0.128 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 4 Day 1, 5 minutes Post-Dose | 22.9 ug/mL | Standard Deviation 4.6 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 5 Day 1, 5 minutes Post-Dose | 22.5 ug/mL | Standard Deviation 3.32 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 14 Day 1, Pre-Dose | 1.60 ug/mL | Standard Deviation 0.6 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 14 Day 1, 5 minutes Post-Dose | 37.0 ug/mL | Standard Deviation 7.92 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 15 Day 1, Pre-Dose | 1.48 ug/mL | Standard Deviation 0.542 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 15 Day 1, 5 minutes Post-Dose | 40.3 ug/mL | Standard Deviation 10.6 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 16 Day 1, Pre-Dose | 1.52 ug/mL | Standard Deviation 0.361 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 1, 5 Minutes Post-Dose | 31.8 ug/mL | Standard Deviation 12.4 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 2 Day 1, Pre-Dose | 0.395 ug/mL | Standard Deviation 0.322 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 2 Day 2, 24 Hours Post-Dose | 10.4 ug/mL | Standard Deviation 8.05 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 2 Day 3, 48 Hours Post-Dose | 11.4 ug/mL | Standard Deviation 16.8 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 2 Day 5, 96 Hours Post-Dose | 9.61 ug/mL | Standard Deviation 17.9 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 4 Day 1, 5 minutes Post-Dose | 30.0 ug/mL | Standard Deviation 12.2 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 5 Day 1, Pre-Dose | 0.845 ug/mL | Standard Deviation 0.564 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 7 Day 1, 5 minutes Post-Dose | 32.3 ug/mL | Standard Deviation 15.4 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 8 Day 1, Pre-Dose | 1.25 ug/mL | Standard Deviation 0.565 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 8 Day 1, 5 minutes Post-Dose | 35.2 ug/mL | Standard Deviation 10.5 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 8 Day 2, 24 Hours Post-Dose | 14.0 ug/mL | Standard Deviation 4.55 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 8 Day 3, 48 Hours Post-Dose | 9.53 ug/mL | Standard Deviation 2.96 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 8 Day 5, 96 Hours Post-Dose | 6.44 ug/mL | Standard Deviation 2.35 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 8 Day 14, 312 Hours Post-Dose | 3.30 ug/mL | Standard Deviation 4.63 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 9 Day 1, Pre-Dose | 4.37 ug/mL | Standard Deviation 11.7 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 9 Day 1, 5 Minutes Post-Dose | 29.6 ug/mL | Standard Deviation 11.3 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 10 Day 1, Pre-Dose | 1.20 ug/mL | Standard Deviation 0.455 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 1, Pre-Dose | NA ug/mL | — |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 10 Day 1, 5 minutes Post-Dose | 35.7 ug/mL | Standard Deviation 9.5 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 2, 24 Hours Post-Dose | 13.0 ug/mL | Standard Deviation 5.34 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 3, 48 Hours Post-Dose | 12.0 ug/mL | Standard Deviation 16.3 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 5, 96 Hours Post-Dose | 8.68 ug/mL | Standard Deviation 13.4 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 1 Day 14, 312 Hours Post-Dose | 2.19 ug/mL | Standard Deviation 3.44 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 2 Day 1, 5-minutes Post-Dose | 32.9 ug/mL | Standard Deviation 9.8 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 3 Day 1, Pre-Dose | 0.491 ug/mL | Standard Deviation 0.387 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 3 Day 1, 5 minutes Post-Dose | 31.3 ug/mL | Standard Deviation 9.79 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 4 Day 1, Pre-dose | 0.691 ug/mL | Standard Deviation 0.492 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 5 Day 1, 5 minutes Post-Dose | 30.6 ug/mL | Standard Deviation 15.1 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 6 Day 1, Pre-Dose | 1.06 ug/mL | Standard Deviation 0.699 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 6 Day 1, 5 minutes Post-Dose | 33.2 ug/mL | Standard Deviation 16.1 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 7 Day 1, Pre-Dose | 1.04 ug/mL | Standard Deviation 0.618 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 16 Day 1, 5 minutes Post-Dose | 41.5 ug/mL | Standard Deviation 4.7 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 11 Day 1, Pre-Dose | 1.84 ug/mL | Standard Deviation 1.57 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 11 Day 1, 5 minutes Post-Dose | 35.7 ug/mL | Standard Deviation 10.8 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 12 Day 1, Pre-Dose | 1.47 ug/mL | Standard Deviation 0.665 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 12 Day 1, 5 minutes Post-Dose | 40.0 ug/mL | Standard Deviation 10.4 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 13 Day 1, Pre-Dose | 6.28 ug/mL | Standard Deviation 11.5 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) | Cycle 13 Day 1, 5 minutes Post-Dose | 33.3 ug/mL | Standard Deviation 16.1 |
Secondary
Duration of Response (DOR) (Phase 1 and 2)
DOR is defined as the time in months from the date of first documentation of a CR or PR to the date of first documentation of tumor progression or PD per IRF assessment according to IWG criteria or to death due to any cause, whichever comes first. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir.
Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)
Population: Participants with response from the Safety Population, all enrolled participants who received at least one dose of brentuximab vedotin, with data available for analysis. Duration of response was censored at last observation documenting absence of PD for participants who did not have tumor progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Duration of Response (DOR) (Phase 1 and 2) | NA months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Duration of Response (DOR) (Phase 1 and 2) | 30.3 months |
Secondary
Event Free Survival (EFS) (Phase 1 and 2)
EFS is defined as the time in months from first dose until any cause of treatment failure: disease progression, premature discontinuation of treatment for any reason, or death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir.
Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)
Population: Safety population is defined as all participants who received at least 1 dose of study drug. EFS was censored on the last follow-up date if none of the above events occur during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Event Free Survival (EFS) (Phase 1 and 2) | 2.7 months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Event Free Survival (EFS) (Phase 1 and 2) | 2.1 months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Event Free Survival (EFS) (Phase 1 and 2) | 4.8 months |
Secondary
Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2)
Blood samples were collected and tested for MMAE plasma concentrations.
Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose
Population: PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Cycle 2 Day 2 values are collected in phase 1 participants only. Here, number analyzed is number of participants assessed at given time-point. Data summarized together for all participants in brentuximab vedotin 1.8 mg/kg arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 1, 5 Minutes Post-Dose | 0.416 ng/mL | Standard Deviation 0.48 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 2 Day 5, 96 Hours Post-Dose | 2.60 ng/mL | Standard Deviation 1.04 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 2 Day 2, 24 Hours Post-Dose | 5.63 ng/mL | Standard Deviation 5.72 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 14, 312 Hours Post-Dose | 0.196 ng/mL | Standard Deviation 0.0641 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 3 Day 1, Pre-Dose | 0.0250 ng/mL | Standard Deviation 0.0354 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 4 Day 1, 5 minutes Post-Dose | 0.234 ng/mL | Standard Deviation 0.0742 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 3, 48 Hours Post-Dose | 4.20 ng/mL | Standard Deviation 1.95 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 5 Day 1, Pre-Dose | 0.0820 ng/mL | — |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 3 Day 1, 5 minutes Post-Dose | 0.216 ng/mL | Standard Deviation 0.0361 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 5 Day 1, 5 minutes Post-Dose | 0.334 ng/mL | Standard Deviation 0.0955 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 2 Day 1, Pre-Dose | 0.0647 ng/mL | Standard Deviation 0.0358 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 6 Day 1, Pre-Dose | 0.0680 ng/mL | Standard Deviation 0.0156 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 7 Day 1, Pre-Dose | 0.104 ng/mL | Standard Deviation 0.0389 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 4 Day 1, Pre-dose | 0.0565 ng/mL | Standard Deviation 0.00495 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 7 Day 1, 5 minutes Post-Dose | 0.326 ng/mL | Standard Deviation 0.0361 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 2, 24 Hours Post-Dose | 4.63 ng/mL | Standard Deviation 3.2 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 6 Day 1, 5 minutes Post-Dose | 0.247 ng/mL | Standard Deviation 0.00707 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 2 Day 1, 5-minutes Post-Dose | 0.556 ng/mL | Standard Deviation 0.562 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 5, 96 Hours Post-Dose | 2.80 ng/mL | Standard Deviation 0.3 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 2 Day 3, 48 Hours Post-Dose | 4.60 ng/mL | Standard Deviation 3.7 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 1, Pre-Dose | NA ng/mL | — |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 9 Day 1, 5 Minutes Post-Dose | 0.218 ng/mL | Standard Deviation 0.128 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 10 Day 1, Pre-Dose | 0.727 ng/mL | Standard Deviation 0.0517 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 10 Day 1, 5 minutes Post-Dose | 0.204 ng/mL | Standard Deviation 0.0982 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 11 Day 1, Pre-Dose | 0.0763 ng/mL | Standard Deviation 0.0368 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 11 Day 1, 5 minutes Post-Dose | 0.255 ng/mL | Standard Deviation 0.133 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 12 Day 1, Pre-Dose | 0.105 ng/mL | Standard Deviation 0.0983 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 14 Day 1, 5 minutes Post-Dose | 0.320 ng/mL | Standard Deviation 0.138 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 15 Day 1, Pre-Dose | 0.0843 ng/mL | Standard Deviation 0.0548 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 15 Day 1, 5 minutes Post-Dose | 0.404 ng/mL | Standard Deviation 0.192 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 16 Day 1, Pre-Dose | 0.139 ng/mL | Standard Deviation 0.0926 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 16 Day 1, 5 minutes Post-Dose | 0.381 ng/mL | Standard Deviation 0.277 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 2 Day 2, 24 Hours Post-Dose | 3.71 ng/mL | Standard Deviation 3.94 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 4 Day 1, Pre-dose | 0.0866 ng/mL | Standard Deviation 0.0784 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 4 Day 1, 5 minutes Post-Dose | 0.376 ng/mL | Standard Deviation 0.449 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 5 Day 1, Pre-Dose | 0.0862 ng/mL | Standard Deviation 0.0729 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 5 Day 1, 5 minutes Post-Dose | 0.301 ng/mL | Standard Deviation 0.248 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 7 Day 1, Pre-Dose | 0.0830 ng/mL | Standard Deviation 0.0578 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 7 Day 1, 5 minutes Post-Dose | 0.310 ng/mL | Standard Deviation 0.282 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 8 Day 5, 96 Hours Post-Dose | 2.00 ng/mL | Standard Deviation 1.05 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 12 Day 1, 5 minutes Post-Dose | 0.252 ng/mL | Standard Deviation 0.116 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 13 Day 1, Pre-Dose | 0.110 ng/mL | Standard Deviation 0.0629 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 13 Day 1, 5 minutes Post-Dose | 0.244 ng/mL | Standard Deviation 0.13 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 14 Day 1, Pre-Dose | 0.109 ng/mL | Standard Deviation 0.0529 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 1, Pre-Dose | NA ng/mL | — |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 1, 5 Minutes Post-Dose | 0.368 ng/mL | Standard Deviation 0.309 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 2, 24 Hours Post-Dose | 4.88 ng/mL | Standard Deviation 3.55 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 3, 48 Hours Post-Dose | 5.36 ng/mL | Standard Deviation 3.72 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 5, 96 Hours Post-Dose | 4.43 ng/mL | Standard Deviation 3.04 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 1 Day 14, 312 Hours Post-Dose | 0.530 ng/mL | Standard Deviation 0.552 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 2 Day 1, Pre-Dose | 0.0739 ng/mL | Standard Deviation 0.064 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 2 Day 1, 5-minutes Post-Dose | 0.478 ng/mL | Standard Deviation 0.461 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 2 Day 3, 48 Hours Post-Dose | 3.86 ng/mL | Standard Deviation 3.18 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 2 Day 5, 96 Hours Post-Dose | 2.70 ng/mL | Standard Deviation 1.69 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 3 Day 1, Pre-Dose | 0.0650 ng/mL | Standard Deviation 0.059 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 3 Day 1, 5 minutes Post-Dose | 0.514 ng/mL | Standard Deviation 0.684 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 6 Day 1, Pre-Dose | 0.0841 ng/mL | Standard Deviation 0.0632 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 6 Day 1, 5 minutes Post-Dose | 0.450 ng/mL | Standard Deviation 0.663 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 8 Day 1, Pre-Dose | 0.101 ng/mL | Standard Deviation 0.934 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 8 Day 1, 5 minutes Post-Dose | 0.295 ng/mL | Standard Deviation 0.151 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 8 Day 2, 24 Hours Post-Dose | 1.96 ng/mL | Standard Deviation 1.31 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 8 Day 3, 48 Hours Post-Dose | 1.91 ng/mL | Standard Deviation 1.29 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 8 Day 14, 312 Hours Post-Dose | 0.325 ng/mL | Standard Deviation 0.214 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) | Cycle 9 Day 1, Pre-Dose | 0.0819 ng/mL | Standard Deviation 0.0496 |
Secondary
Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2)
Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
Time frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months)
Population: Safety population is defined as all participants who received at least 1 dose of study drug. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | C-reactive protein increased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | White blood cell count decreased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Weight decreased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Blood bicarbonate decreased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Gamma-glutamyltransferase increased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Alanine aminotransferase increased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Lymphocyte count decreased | 1 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Aspartate aminotransferase increased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Blood alkaline phosphatase increased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Neutrophil count decreased | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Transaminases increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Blood bicarbonate decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Alanine aminotransferase increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Aspartate aminotransferase increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Lymphocyte count decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Neutrophil count decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | White blood cell count decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Weight decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | C-reactive protein increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Blood alkaline phosphatase increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Gamma-glutamyltransferase increased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Transaminases increased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Gamma-glutamyltransferase increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | C-reactive protein increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Lymphocyte count decreased | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Alanine aminotransferase increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Blood alkaline phosphatase increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Aspartate aminotransferase increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Blood bicarbonate decreased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | White blood cell count decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Transaminases increased | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Weight decreased | 1 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) | Neutrophil count decreased | 2 Participants |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Time frame: From the first dose through 30 days after the last dose of study medication (up to 15 months)
Population: Safety population is defined as all participants who received at least 1 dose of study drug. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) | SAEs | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) | TEAEs | 3 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) | TEAEs | 16 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) | SAEs | 7 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) | TEAEs | 17 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) | SAEs | 1 Participants |
Secondary
Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2)
Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA and nATA development) using a laboratory test. ATA-positive samples were further characterized as transiently ATA positive (defined as 1 or 2 post-Baseline ATA-positive responses), persistently ATA positive (defined as more than 2 post-Baseline ATA positive responses), and nATA positive or negative.
Time frame: Baseline up to EOT (Up to 15 months)
Population: Participants from the Safety Population, all enrolled participants who received at least one dose of brentuximab vedotin, with data available for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) | ATA status: Transiently positive | 1 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) | ATA status: Persistently positive | 0 Participants |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) | nATA status: Positive | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) | nATA status: Positive | 5 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) | ATA status: Persistently positive | 2 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) | ATA status: Transiently positive | 4 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) | ATA status: Persistently positive | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) | nATA status: Positive | 4 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) | ATA status: Transiently positive | 7 Participants |
Secondary
Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2)
Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.
Time frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months)
Population: Safety population is defined as all participants who received at least 1 dose of study drug. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2) | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2) | 0 Participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2) | 0 Participants |
Secondary
Overall Response Rate (ORR) (Phase 1)
Overall response rate is defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)
Population: Response-evaluable population included participants who received at least 1 dose of study drug, have measurable disease at baseline, and 1 postbaseline disease assessment. Participants enrolled in Phase 1 of the study were evaluated for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Overall Response Rate (ORR) (Phase 1) | 0 percentage of participants |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Overall Response Rate (ORR) (Phase 1) | 63 percentage of participants |
Secondary
Overall Survival (OS) (Phase 1 and 2)
OS is the time in months from start of study treatment to date of death due to any cause.
Time frame: Every 6 months after EOT, until the sooner of death, study closure, or 2 years after enrolment of the last participant (Up to 72 months)
Population: Safety population is defined as all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Overall Survival (OS) (Phase 1 and 2) | NA months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Overall Survival (OS) (Phase 1 and 2) | NA months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Overall Survival (OS) (Phase 1 and 2) | NA months |
Secondary
Progression Free Survival (PFS) (Phase 1 and 2)
PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir.
Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)
Population: Safety population is defined as all participants who received at least 1 dose of study drug. PFS was censored on the day following the date of last radiological assessment of measured lesions documenting absence of PD for participants who did not have tumor progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Progression Free Survival (PFS) (Phase 1 and 2) | 2.7 months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Progression Free Survival (PFS) (Phase 1 and 2) | 3.8 months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Progression Free Survival (PFS) (Phase 1 and 2) | 6.2 months |
Secondary
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Blood samples were collected and tested for conjugated and unconjugated antibodies.
Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose
Population: PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Cycle 2 Day 2 values are collected in phase 1 participants only. Here, number analyzed is number of participants assessed at given time-point. Data summarized together for all participants in brentuximab vedotin 1.8 mg/kg arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 6 Day 1, Pre-Dose | 1.05 ug/mL | Standard Deviation 1.2 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 1, 5 Minutes Post-Dose | 26.3 ug/mL | Standard Deviation 2.29 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 2, 24 Hours Post-Dose | 16.7 ug/mL | Standard Deviation 1.5 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 3, 48 Hours Post-Dose | 12.7 ug/mL | Standard Deviation 3.13 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 5, 96 Hours Post-Dose | 8.63 ug/mL | Standard Deviation 5.11 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 4 Day 1, 5 minutes Post-Dose | 29.6 ug/mL | Standard Deviation 8.13 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 5 Day 1, Pre-Dose | 0.844 ug/mL | Standard Deviation 0.928 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 5 Day 1, 5 minutes Post-Dose | 29.4 ug/mL | Standard Deviation 3.04 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 1, Pre-Dose | NA ug/mL | — |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 6 Day 1, 5 minutes Post-Dose | 29.4 ug/mL | Standard Deviation 5.37 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 7 Day 1, Pre-Dose | 0.995 ug/mL | Standard Deviation 0.998 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 7 Day 1, 5 minutes Post-Dose | 24.0 ug/mL | Standard Deviation 2.69 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 13 Day 1, 5 minutes Post-Dose | NA ug/mL | — |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 14, 312 Hours Post-Dose | 2.23 ug/mL | Standard Deviation 0.833 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 1, Pre-Dose | 0.470 ug/mL | Standard Deviation 0.459 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 1, 5-minutes Post-Dose | 26.9 ug/mL | Standard Deviation 7.98 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 2, 24 Hours Post-Dose | 17.1 ug/mL | Standard Deviation 10.4 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 3, 48 Hours Post-Dose | 9.60 ug/mL | Standard Deviation 5.39 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 3, 96 Hours Post-Dose | 6.43 ug/mL | Standard Deviation 3.69 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 3 Day 1, Pre-Dose | 0.415 ug/mL | Standard Deviation 0.586 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 3 Day 1, 5 minutes Post-Dose | 30.0 ug/mL | Standard Deviation 5.87 |
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 4 Day 1, Pre-dose | 0.875 ug/mL | Standard Deviation 1.03 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 8 Day 1, 5 minutes Post-Dose | 41.4 ug/mL | Standard Deviation 9.47 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 7 Day 1, 5 minutes Post-Dose | 41.0 ug/mL | Standard Deviation 21.2 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 8 Day 1, Pre-Dose | 3.29 ug/mL | Standard Deviation 1.14 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 8 Day 3, 48 Hours Post-Dose | 22.9 ug/mL | Standard Deviation 5.67 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 8 Day 5, 96 Hours Post-Dose | 17.3 ug/mL | Standard Deviation 4.93 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 8 Day 14, 312 Hours Post-Dose | 5.74 ug/mL | Standard Deviation 2.02 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 9 Day 1, Pre-Dose | 6.30 ug/mL | Standard Deviation 12 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 9 Day 1, 5 Minutes Post-Dose | 35.1 ug/mL | Standard Deviation 11.3 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 10 Day 1, Pre-Dose | 3.48 ug/mL | Standard Deviation 1.13 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 10 Day 1, 5 minutes Post-Dose | 41.4 ug/mL | Standard Deviation 8.63 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 11 Day 1, Pre-Dose | 3.96 ug/mL | Standard Deviation 2.24 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 11 Day 1, 5 minutes Post-Dose | 42.8 ug/mL | Standard Deviation 8.85 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 12 Day 1, Pre-Dose | 3.47 ug/mL | Standard Deviation 1.28 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 12 Day 1, 5 minutes Post-Dose | 44.8 ug/mL | Standard Deviation 10.3 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 13 Day 1, Pre-Dose | 11.3 ug/mL | Standard Deviation 17.1 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 3, 48 Hours Post-Dose | 16.0 ug/mL | Standard Deviation 6.73 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 13 Day 1, 5 minutes Post-Dose | 40.3 ug/mL | Standard Deviation 19.2 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 14 Day 1, Pre-Dose | 3.97 ug/mL | Standard Deviation 1.14 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 14 Day 1, 5 minutes Post-Dose | 44.5 ug/mL | Standard Deviation 7.05 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 15 Day 1, Pre-Dose | 4.02 ug/mL | Standard Deviation 1.4 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 15 Day 1, 5 minutes Post-Dose | 49.7 ug/mL | Standard Deviation 6.88 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 16 Day 1, Pre-Dose | 4.60 ug/mL | Standard Deviation 1.67 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 1, Pre-Dose | NA ug/mL | — |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 16 Day 1, 5 minutes Post-Dose | 49.7 ug/mL | Standard Deviation 7.61 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 1, 5 Minutes Post-Dose | 34.7 ug/mL | Standard Deviation 13.4 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 5, 96 Hours Post-Dose | 11.8 ug/mL | Standard Deviation 5.02 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 2, 24 Hours Post-Dose | 25.0 ug/mL | Standard Deviation 9.59 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 3 Day 1, 5 minutes Post-Dose | 38.2 ug/mL | Standard Deviation 13.1 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 3, 48 Hours Post-Dose | 18.5 ug/mL | Standard Deviation 7.57 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 14, 312 Hours Post-Dose | 3.50 ug/mL | Standard Deviation 1.7 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 4 Day 1, Pre-dose | 1.95 ug/mL | Standard Deviation 1.26 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 3, 96 Hours Post-Dose | 10.2 ug/mL | Standard Deviation 5.16 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 4 Day 1, 5 minutes Post-Dose | 37.1 ug/mL | Standard Deviation 15.6 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 1, Pre-Dose | 1.16 ug/mL | Standard Deviation 0.825 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 5 Day 1, Pre-Dose | 2.45 ug/mL | Standard Deviation 1.68 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 8 Day 2, 24 Hours Post-Dose | 28.2 ug/mL | Standard Deviation 6.38 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 5 Day 1, 5 minutes Post-Dose | 38.0 ug/mL | Standard Deviation 18.8 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 1, 5-minutes Post-Dose | 35.6 ug/mL | Standard Deviation 12 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 6 Day 1, Pre-Dose | 2.99 ug/mL | Standard Deviation 1.81 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 3 Day 1, Pre-Dose | 1.62 ug/mL | Standard Deviation 1.07 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 6 Day 1, 5 minutes Post-Dose | 39.8 ug/mL | Standard Deviation 19.8 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 2, 24 Hours Post-Dose | 17.2 ug/mL | Standard Deviation 7.93 |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 7 Day 1, Pre-Dose | 2.92 ug/mL | Standard Deviation 1.62 |
Secondary
Time to Progression (TTP) (Phase 1 and 2)
TTP is defined as the time in months from first dose until the first subsequent documentation of objective tumor progression. Progressive disease (PD) is defined as any new lesion or increase by ≥50% of previously involved sites from nadir.
Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)
Population: Safety population is defined as all participants who received at least 1 dose of study drug. TTP was censored on last radiological assessment of measured lesions documenting absence of PD for participants who did not have tumor progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Time to Progression (TTP) (Phase 1 and 2) | 2.7 months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Time to Progression (TTP) (Phase 1 and 2) | 4.8 months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Time to Progression (TTP) (Phase 1 and 2) | 6.2 months |
Secondary
Time to Response (Phase 1 and 2)
Time to response is defined as the time in months from the first dose of study treatment until the date of the first assessment of confirmed CR or PR. as assessed by an IRF using IWG revised response criteria for malignant lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)
Population: Response-evaluable population included participants who received at least 1 dose of study drug, have measurable disease at baseline, and 1 postbaseline disease assessment. Time to response was censored on the last radiological assessment of measured lesions documenting absence of CR or PR for participants who did not have CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Time to Response (Phase 1 and 2) | NA months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 | Time to Response (Phase 1 and 2) | 2.7 months |
| Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Time to Response (Phase 1 and 2) | 1.5 months |